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Diagnostics and Personalised Healthcare
Daniel O’Day | Chief Operating OfficerRoche Diagnostics
Roche Diagnostics: Uniquely Positioned
Revaluing in vitro Diagnostics
Driving Personalised Healthcare
Number 1 in IVD… … a large and growing market
9%12%
Professional 5%
6%41
54$bn CAGR
5%
3%4%
7%
10%12%12%
20%
RocheAbbott
Siemens J&J
Beckman Coulter
bioMérieuxBayer
IVD = in vitro diagnostics Source: Boston Biomedical Consultants, Company reports, Roche analysis
2008 2013E
3.02
9
28
MolecularTissue
53
Diabetes11
35
Roche DiagnosticsLeader in a growing market
Strong presence and broad portfolio Solid basis for future growth
Present in all customer segments
HospitalRef. Lab ER/ ICU
Doc. OfficeAcademia
PharmaPatient
Broad array of technologies
Chemistry & ELISA Arrays Sequencing
IHC/ ISH PCR Cellular analysis
Large installed base
NAMEMEA
Japan
LATAMAPAC
Increasing # innovative products
0
5
10
15
20
25
2007 2008 2009 2010 E
RTDRASRMDRDCRPD
Roche Diagnostics: Uniquely Positioned
Revaluing in vitro Diagnostics
Driving Personalised Healthcare
European Diagnostic Manufacturers Association (EDMA) 2009
IVD <2 % total worldwide healthcare spendInfluences >60 % of critical decision making
medical value
Opportunity to revalue Diagnostics
Medical breakthroughs and market demographics Increasing the importance of Diagnostics
Need for personalisedhealthcare
Advances in science enabling new insights
Unmet medical need,Market demographics
Medical Value
• Screening• Diagnosis• Prognosis• Prediction• Monitoring
• Treatment selection• Response prediction• Treatment monitoring
Diagnostics
Companion Diagnostics
Creating medical value Beyond diagnosis … to Personalised Healthcare
+
Increasing barriers to entry
Content Development
Roche Pharma
External research
In-house research
IVD SystemDevelopment
Reagent kits
Hardware
Software
Technicalvalidation
ClinicalValidation
Demonstrateclinical utility
Healtheconomic data
Regulatory submission
Clinical Adoption
Reimburse-ment/ Premium pricing
Market uptakevia clinicians
Medical guidelines
Medical value requires new capabilities Roche uniquely positioned to capture the value
Roche’s distinctivenessSignificant advantages to both businesses
• new content• patient samples• clinical trials• testing demand• platform adoption
• biomarkers • tools & technologies• validated assays• regulatory expertise• commercial reach
Diagnostics
Medical value products
Pharma
Efficient & safe medicines
IP
Roche Diagnostics: Uniquely Positioned
Revaluing in vitro Diagnostics
Driving Personalised Healthcare
Creating medical value Through new diagnostics tests…
Medical Value
• Screening• Diagnosis• Prognosis• Prediction• Monitoring
• Treatment selection• Response prediction• Treatment monitoring
Diagnostics
Companion Diagnostics
+
Number of HPV tests in the US
~1 m
~28 m
~50 m
Clinical Applications
U.S. Market:$250 m, 20%
growth per year
Pap HPV Colposcopy+ +
- 1 year
Pap/HPV
+ +
+ 1 year
3 years
Colposcopy
HPV Pap+ +
- 3 years
Colposcopy
ASCUS Triage
Adjunct screening
Primary screening
-- -
Cervical Cancer: HPV screening algorithmsGrowth and market size driven by adoption of screening
Company reports, Roche analysis
The ATHENA Trial
~47,000 womenFollow-UpYear 1
Follow-UpYear 2
Follow-UpYear 3
2009 - 2010 2010 - 2011 2011 - 2012
Enrolment Completed
ATHENA trial demonstrates medical value of HPV testing and Genotyping in Cervical Cancer screening
• Targets ASCUS triage, adjunct screening and HPV 16/18 claims
• Study results confirm variability of cytology and support improved consistency of HPV DNA based cervical cancer screening programs
• Data support HPV 16/18 genotyping as actionable information for intervention
• FDA submission mid 2010; data to be presented at IPV, Montreal 07/2010
* Wright, TC., EUROGIN 2010
Women with colposcopy (~8,000)
2009
ASCUS/ HPV+
Pap-/ 16/18+Pap-/ HPV +Pap-/ HPV - ASCUS/ 16/18+
ASCUS/ HPV-
Deferred follow up Yearly follow up Immediate
follow up
4.5%5.7%6.1%6.5%CIN 2+ overall
15.5%15.6%15.7%13.8%HR HPV Positive
9.8%8.1%5.2%3.7%Cytology Abnormal
DCBASite
Increasing risk of CIN2+
Cytology vs. HPV Testing*
Immediate follow up for HPV 16/18
ATHENA establishes the value of genotyping in cervical cancer
screening programs2 % 10 %
Preeclampsia: A significant unmet clinical needPlGF and sFlt1 - first IVD tests for Preeclampsia
• Leading cause of fetal and maternal death
• Until recently, no specific tests available
• Roche developed first automated test to diagnose women with preeclampsia by measuring PlGF and sFlt levels2
• Early detection of patients at risk allows closer prenatal monitoring, early diagnosis and timely intervention
sFlt-1 = soluble fms-like tyrosine kinase; PIGF = placental growth factor1 World Health Organisation 2 available ex-US
• occurs in 3%-7% of pregnancies
• responsible for 18% of all maternal deaths in US1
• costs more than $7 bn in healthcare annually in US1
Preeclampsia
* p < 0.05
Verlohren et al., Am J of Obstetics and Gynecology, 2010
sFlt1
/ Pl
GF
ratio
Overall survival from Prostate cancer*
70%, n=311
Normal
5’ Deletion
5’ Deletion/ 3’ Duplication
Surv
ival
from
Pro
stat
e C
ance
r %
* Oncogene (2008) 27, 253-263TMPRSS2= transmembrane protease, serine 2 (androgen responsive gene) ERG=Ets Related Gene
Rearrangement status may determine clinical outcome
• How aggressive is my cancer?
• What should the course of my primary therapy be?
• What is my risk of metastasis?
Prostate Cancer: Rearrangements between TMPRSS2 and ERG genes found in ~50% of prostate cancer patients
Ventana BenchMark ULTRA
Assay in development for ERG gene rearrangementsIdentifying prostate cancer aggressiveness for appropriate treatment
Imaged Slide Review for Pathologist
5’ Deletion Likely Aggressive
Normal Likely Indolent
5’ Deletion and 3’ Duplication Highly Aggressive
Prostate cancer diagnosis via H&E
3’ InsertionLikely Aggressive
Ventana SYMPHONY
Oncologist Surgeon
Patient tumor needle biopsy
Creating medical value Through Companion Diagnostics…
Medical Value
• Screening• Diagnosis• Prognosis• Prediction• Monitoring
• Treatment selection• Response prediction• Treatment monitoring
Diagnostics
Companion Diagnostics
+
Strong pipeline of companion diagnosticsJoint Pharma and Diagnostics programs - Oncology
TheraScreen EGFR mutation testEGFRTarceva
TheraScreen KRAS mutation testKRASRG7167 MEK Inh/CIF
PIK3CA
Her1, 2, 3AREG, BTC
MDM2
p53
BRAF
Biomarker
RG7321 PI3K InhRG7422 PI3K Inh
RG1273 PertuzumabRG3502 T-DM1
RG7112 MDM2 Antagonist
RG7112 MDM2 Antagonist
RG7204 BRAF Inh/PLX4032RG7167 MEK Inh/CIF
Pipeline Drug
PCR PIK3CA mutationsFISH PIK3CA copy number assay
cobas MDM2 expression assay
cobas 4800 HER Family expression assay
AmpliChip p53 array
cobas 4800 BRAF V600E test
Pipeline Assay
List not exhaustive
Roche Pharma targeting multiple pathways
Molecular Tests for assessing presence of mutations offers opportunities to tailor treatment
PIP2PIP2
PPPP
PIP3PIP3
PPPP PP
SurvivalSurvival
RTK
PP
PP
PP
PP
RTK
FasL
FasL
ForkheadForkheadPP
AKTAKT
Cell cycle progression and
proliferation
Cell cycle progression and
proliferation
Cyclin D1Cyclin D1
p85p85p110ap110a
PP
PP
PTENPTEN
BadBad
p27
p27
PP
Bcl-2Bcl-2
mTORmTOR
Protein synthesis
and growth
Protein synthesis
and growth
PP
TSC1
TSC1
TSC2
TSC2
PP
PI3KPI3K
mTOR
AKT
RasRas
ERKERKPP
RafRafPP
MEKMEKPP
Raf
MEK
Mutation in BRAF KinaseCo-development of test and drug in oncology
• Identifies patients whose tumor DNA carries BRAFV600E mutation
• Increases feasibility of drug clinical development and probability of success
• IVD timelines aligned with RG7204 accelerated development plan → joint launch
* BRAF gene mutations detected in ~8% of all cancers, over 50% of malignant melanomas
Single mutation in BRAF gene (BRAFV600E) causes activation in absence of normal growth factor stimulation
Sample collection &
DNA extraction
BRAFV600E
+ve?
YES
RG7204
Roche Real time PCR
cobas 4800
∼3 hrs
AmpliChip p53 and MDM2 Antagonist Identifying patients with non-mutated tumor suppressor protein
* approx. 50% human tumors contain p53 mutants
• Blocking MDM2/ p53 binding enables p53 activity
• MDM2 antagonist (RG7112) may require wild-type p53*
Tumor growth
p53MDM2
Tumor regression
MDM2 antagonist
MDM2MDM2
p53
p53MDM2X
X
• Parallel development of AmpliChip p53 array
• Identifies patients with wild-type p53 gene
• Essential for RG7112 clinical development
Serum markers and LebrikizumabMay identify asthma patients most likely to respond
• Need for non-invasive surrogate markers
• Serum Periostin, IgE and CEA - alone or combined - may predict drug response
• Potential to identify sub-population with improved clinical response to lebrikizumab (anti-IL-13)
Two distinct Asthma sub-groups
• Early Roche Diagnostics - gREDcollaboration ensures timely availability of assays for trial program
• Enables patient stratification
• Combining multiple biomarkers may improve sensitivity & specificity
PeriostinIgE CEA
Strong pipeline of innovative Diagnostics and Companion Dx tests
Combined strengths of Roche Pharma and Diagnostics to lead Personalised Healthcare
Uniquely positioned to revalue Diagnostics through delivery of medical value
PIP2PIP2
PP
PP
PIP3PIP3
PP
PP
PP
Survival
Survival
RTK
P
P
P
P
P
P
P
P
RTK
FasL
FasL
ForkheadForkhead
P
P
AKTAKT
Cell cycle progression and proliferation
Cell cycle progression and proliferation
Cyclin D1Cyclin D1
p85p85p110ap110a
P
P
P
P
PTENPTEN
BadBad
p27
p27
P
P
Bcl-2Bcl-2
mTORmTOR
Protein synthesis
and growth
Protein synthesis
and growth
P
P
TSC1TSC1
TSC2TSC2
P
P
PI3KPI3K
mTOR
AKT
ERKERK
PP
RafRaf
PP
MEKMEK
PP
Raf
MEK
RasRas
Roche Diagnostics Driving future value for Roche